Plasma membrane glycolipids serve as primary attachment sites for a broad range of infectious and amyloid proteins (Fantini, 2003). For instance, both GM1 and GM3 gangliosides have been involved in the pathophysiology of Alzheimer's and Parkinson's diseases (Oikawa et al, 2009; Wu et al, 2012).
In a recent study of the glycolipid binding specificity of α-synuclein, the protein associated with Parkinson's disease, Fantini et al identified the 34-45 fragment of the protein as the shortest active glycolipid binding domain (Fantini and Yahi, 2011a). This short linear motif of 12 amino acid residues confers to the protein a high specificity of interaction for GM3, a ganglioside preferentially expressed by astrocytes. This motif shares structural homology with the 5-16 fragment of Alzheimer's β-amyloid peptide (Aβ). Yet the glycolipid-binding domain of Aβ does not recognize GM3, but GM1, a ganglioside abundantly expressed at the level of post-synaptic membranes.